RESUMO
Mechanisms that regulate the growth and form of the vertebrate skeleton are largely unknown. The zebrafish mutant rapunzel has heterozygous defects in bone development, resulting in skeletal overgrowth, thus identification of the genetic lesion underlying rapunzel might provide insight into the molecular basis of skeletogenesis. In this report, we demonstrate that the rapunzel mutant results from a missense mutation in the previously uncharacterized rpz gene. This conclusion is supported by genetic mapping, identification of a missense mutation in rapunzel(c14) in a highly conserved region of the rpz gene, and suppression of the rapunzel homozygous embryonic phenotype with morpholino knockdown of rpz. In addition, rpz transcripts are identified in regions correlating with the homozygous embryonic phenotype (head, pectoral fin buds, somites and fin fold). This report provides the first gene identification for a mutation affecting segment number in the zebrafish fin and development of both the fin ray (dermal) and the axial skeleton.
Assuntos
Mutação , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Padronização Corporal , Sequência Conservada , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Hibridização In Situ , Dados de Sequência Molecular , Fenótipo , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/metabolismoRESUMO
Vertebrate neural development has been extensively investigated. However, it is unknown for any vertebrate gene how the onset of neural-specific expression in early gastrula embryos is transcriptionally regulated. geminin expression is among the earliest markers of dorsal, prospective neurectoderm at early gastrulation in Xenopus laevis. Here, we identified two 5' sequence domains that are necessary and sufficient to drive neural-specific expression during gastrulation in transgenic Xenopus embryos. Each domain contained putative binding sites for the transcription factor Tcf, which can mediate Wnt signaling and for Vent homeodomain proteins, transcriptional repressors that mediate BMP signaling. Results from embryos transgenic for constructs with mutated Tcf or Vent sites demonstrated that signaling through the Tcf sites was required for dorsal-specific expression at early gastrulation, while signaling through the Vent sites restricted geminin expression to the prospective neurectoderm at mid-gastrulation. Consistent with these results, geminin 5' regulatory sequences and endogenous Xgem responded positively to Wnt signaling and negatively to BMP signaling. The two 5' sequence domains were also conserved among geminin orthologs. Together, these results demonstrate that signaling through Tcf and Vent binding sites regulates transcription of geminin in prospective neurectoderm during gastrulation.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Gástrula/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Neurônios/metabolismo , Fatores de Transcrição TCF/genética , Fatores de Transcrição/genética , Proteínas de Xenopus/genética , Xenopus/embriologia , Animais , Sítios de Ligação/genética , Proteínas de Ciclo Celular/genética , Sequência Conservada , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Evolução Molecular , Gástrula/citologia , Geminina , Proteínas de Homeodomínio/metabolismo , Hibridização In Situ , Modelos Genéticos , Neurônios/citologia , Elementos Reguladores de Transcrição , Transdução de Sinais , Fatores de Transcrição TCF/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Transgenes , Proteína Wnt1/genética , Proteína Wnt1/metabolismo , Xenopus/genética , Xenopus/metabolismo , Proteínas de Xenopus/metabolismoRESUMO
ISSUE ADDRESSED: This paper describes a review of population health social marketing campaigns targeting culturally and linguistically diverse (CLD) communities in Australia in order to identify characteristics of effective CLD campaigns. METHODS: Literature on CLD population health social marketing was identified from electronic searches of databases in August 2004. At the same time, the grey literature was examined by searching the Internet and talking to Australian experts in the fields of CLD social marketing and CLD research. RESULTS: Eight studies met the search criteria, four from the published literature. Two studies that employed prepost evaluation designs provided tentative support for the potential efficacy of CLD social marketing strategies. The remaining studies did not allow for causal attribution as they used post-campaign only or process evaluations. Studies did, however, show that CLD communities access campaign-related information from both mainstream and ethnic media channels. In addition, Vietnamese respondents were more likely to access campaign messages through ethnic radio and Chinese respondents through ethnic press. CONCLUSIONS: There is insufficient evidence to clearly identify the characteristics of effective CLD campaigns. Campaign evaluation designs used to evaluate social marketing strategies targeting CLD communities in Australia are generally weak, but there is tentative evidence supporting the potential efficacy of these strategies in some Australian settings.
Assuntos
Barreiras de Comunicação , Diversidade Cultural , Promoção da Saúde/métodos , Austrália , Promoção da Saúde/organização & administração , Humanos , Meios de Comunicação de MassaRESUMO
Balancing signals derived from the TGFbeta family is crucial for regulating cell proliferation and differentiation, and in establishing the embryonic axis during development. TGFbeta/BMP signaling leads to the activation and nuclear translocation of Smad proteins, which activate transcription of specific target genes by recruiting P/CAF and p300. The two members of the ZEB family of zinc finger factors (ZEB-1/deltaEF1 and ZEB-2/SIP1) regulate TGFbeta/BMP signaling in opposite ways: ZEB-1/deltaEF1 synergizes with Smad-mediated transcriptional activation, while ZEB-2/SIP1 represses it. Here we report that these antagonistic effects by the ZEB proteins arise from the differential recruitment of transcriptional coactivators (p300 and P/CAF) and corepressors (CtBP) to the Smads. Thus, while ZEB-1/deltaEF1 binds to p300 and promotes the formation of a p300-Smad transcriptional complex, ZEB-2/SIP1 acts as a repressor by recruiting CtBP. This model of regulation by ZEB proteins also functions in vivo, where they have opposing effects on the regulation of TGFbeta family-dependent genes during Xenopus development.